1. Field of the Invention
The present invention relates to isoxazole derivatives useful as, for example, therapeutic drugs for autoimmune diseases, inflammatory diseases, etc.
2. Description of the Related Art
Acidic nonsteroidal anti-inflammatory drugs or steroidal drugs have been used as therapeutic drugs for inflammatory diseases but are limited in their use because of their side effects. In addition, treatments using such drugs, despite their ability to ameliorate symptoms cannot remove the fundamental cause of the diseases. With the progress of elucidation of the pathophysiology of autoimmune diseases such as rheumatoid arthritis accompanied by serious inflammation, it has been suggested that an immune system disorders are deeply concerned in the onset of inflammation, its progression and maintenance of a chronic state. For these reasons, drugs capable of modifying the diseases by acting on the immune system, such as gold compounds and D-penicillamine have been noted as drugs for causal treatment. They, however, are not always satisfactory because of their side effects and deficiency in lasting efficacy.
On the other hand, isoxazole derivatives having various biological activities have been reported. For example, Japanese Patent Unexamined Publication No. 63-152368 reports aralkyl 5-membered heterocyclic compounds including isoxazole derivatives, as therapeutic drugs for autoimmune diseases, inflammation, allergy, asthma, etc. German Patent No. 2847792 reports quinolylguanidine derivatives including isoxazole derivatives, as anti-inflammatory, analgesic and antipyretic drugs. J. Med. Chem. 21, 773(1978) reports that N-cyano-N'-isoxazolylguanidine derivatives are effective as hypotensive drugs.
Therapeutic drugs for autoimmune diseases should be clearly effective against chronic inflammation which induces tissue destruction. Moreover, it is important for them to have inhibitory effect on an immune system disorders responsible for the diseases, as a drug for radical treatment. In addition, the therapeutic drugs for the diseases should have little adverse side effect because they often require long-term administration.
The present invention is intended to provide a compound useful as a therapeutic or prophylactic drug for autoimmune diseases, inflammatory diseases, etc., which has excellent immunomodulating and anti-choronic-inflammatory effects and has little side effect.